Method for producing optically active 2, 3-bisphosphinopyrazine derivative and method for producing optically active phosphine transition metal complex

Abstract

In the method for producing an optically active 2,3-bisphosphinopyrazine derivative of the present invention, an optically active 2,3-bisphosphinopyrazine derivative represented by the following formula (3) is produced by the step of: preparing solution A containing 2,3-dihalogenopyrazine represented by the following formula (1)and a carboxylic acid amide coordinating solvent, lithiating an optically active R- or S-isomer of a hydrogen-phosphine borane compound represented by the following formula (2)to give a lithiated phosphine borane compound; adding solution B containing the lithiated phosphine borane compound to the solution A to perform an aromatic nucleophilic substitution reaction; and then performing a deboranation reaction.(For symbols in the formulas, see the description.)

Description

TECHNICAL FIELD[0001]The present invention relates to a method for producing a 2,3-bisphosphinopyrazine derivative. More specifically, the present invention relates to a method for producing a 2,3-bisphosphinopyrazine derivative useful as, for example, a ligand for a metal complex used as an asymmetric catalyst in an asymmetric synthetic reaction, and a ligand source for a transition metal complex used as an anticancer agent, and also relates to a method for producing a phosphine transition metal complex useful as an anticancer agent.BACKGROUND ART[0002]Reactions in organic synthesis catalyzed by a metal complex with an optically active phosphine ligand have long been known. These reactions are very useful, on which many research results have been reported. In recent years, ligands in which phosphorus atoms themselves are asymmetric have been developed. For example, Patent Literature 1 and Patent Literature 2 disclose an optically active 2,3-bis(dialkylphosphino)pyrazine derivative ...

AI Technical Summary

Benefits of technology

The present invention provides an industrially advantageous method for producing an optically active 2,3-bisphosphinopyrazine derivative. This method allows for the production of highly pure (S,S) or (R,R) isomers of 2,3-bis(dialkylphosphino)pyrazine derivatives in high yield compared to conventional methods. Additionally, the invention provides a method for producing an optically active phosphine transition metal complex, which is useful as an anticancer agent. The method involves a solution-to-solution reaction between a phosphine borane compound and a 2,3-dihalogenopyrazine derivative in the presence of a carboxylic acid amide coordinating solvent, resulting in the formation of the desired product.

Problems solved by technology

Although the methods disclosed in Patent Literature 1 and Patent Literature 2 can provide the target 2,3-bis(tert-butylmethylphosphino)quinoxaline at good yield and high purity, a special cooling device is required to perform the aromatic nucleophilic substitution reaction at an extremely low temperature of −70° C. or less, and it also takes much time to cool the system to −70° C. or less and to increase the temperature to the temperature at which the subsequent deboranation reaction is performed, and thus the methods are industrially disadvantageous.

However, the problem with the method disclosed in Patent Literature 4 below is that the target (R,R) or (S,S) isomer of a 2,3-bisphosphinopyrazine derivative having high optical purity cannot be obtained at good yield.

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